Leishmania parasite causes human disease (Leishmaniasis) with clinical symptoms ranging from self healing cutaneous lesions to fatal visceral infection. The lack of accurate tools for clinical diagnosis and of a vaccine for leishmaniasis poses a serious health risk for U. S. military personnel, their families and tourists, either living or travelling in endemic areas. In addition, people infected with HIV are particularly prone to be infected by the leishmania parasite. Identifying parasite genes and to develop a vaccine will be beneficial for people at risk of being infected and potentially for patients suffering from the disease. We have developed an in vitro culture system for Leishmania donovani. It allows the transformation of promastigotes to amastigotes and vice versa without going through the sand fly and human macrophage interaction. Parasites grown under such conditions are similar to those isolated from in vivo sources. Using this system, we have (a) identified several parasite genes whose expression is regulated during parasite differentiation, (b) some of the proteins synthesized by these genes elicit antibody responses in patients suffering from leishmaniasis, (c) identified several members of cell cycle regulating genes which are important for the control of parasite growth and (d) expressed cloned parasite genes to develop antibodies which can be used for diagnostic purposes. Currently, detailed analysis of some of the genes is being carried out, with an understanding that it can provide some insight in parasite differentiation and development.